Toxoplasma gondii is an important food borne pathogen due to its ability to infect humans following oral ingestion of cysts found in the tissues of a variety of chronically infected animals. Our previous studies indicate that the ability of tissue cysts to cause direct oral infection is a recently derived trait that gave rise to a rapid and extensive spread of several clonal lineages of the parasite. The central hypothesis explored in this proposal is that the recombination of specific genes gave rise to direct oral transmission in the life cycle of T. gondii. The proposed studies seek to identify the molecular basis of oral infectivity by comparing different genetic lineages of the parasite that either lack or possess the trait of oral infectivity. We will isolate new strains of T. gondii and identify those with unusual genotypes that may represent ancestral forms of the parasite. Exotic strains of T. gondii will be examined to determine their capacity to cause oral infection in vitro and in animal models. The profile of genes expressed by these exotic strains will be examined to determine if they contain or express unique genes. Classical and molecular genetic methods will be employed to identify genes that control oral transmission. The long-term goal of these studies is to elucidate the molecular basis of oral transmission, which may facilitate development of improved detection methods and possible interventions against food borne toxoplasmosis. [unreadable] [unreadable]